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Query: DrugBank:APRD00345 (ICI)
 5,388 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antihypertensive effect of the new beta-blocker, ICI 66,082 was studied in 37 patients with renal or essential hypertension. A daily dose of 75 mg produced a significant antihypertensive effect and a further blood pressure decrease was obtained by increasing the daily dose up to 300 mg; at this treatment level, the antihypertensive effect averaged 29.4/24.0 mm Hg. Increasing the dose from 300 to 600 mg daily did not produce a significant additional blood pressure decrease. Six of the 37 patients retained fluid, producing a loss in the antihypertensive effect. No significant correlation was found between the percentage systolic blood pressure fall and the following parameters determined before therapy: systolic blood pressure and its variability, heart rate (at rest and after stimulation by exercise or isoproterenol), cardiac output and total peripheral resistance, renin concentration (at rest and after stimulation) and urinary excretion of catecholamines and derivates.
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PMID:Predictive value of various parameters for the antihypertensive effect of the beta blocker ICI 66,082 (1). 23 80

The antihypertensive effect of atenolol, a new beta 1 receptor blocking agent, was studied in a double blind non cross-over trial in 40 patients (pts) affected by mild to moderately severe essential hypertension with normal plasma renin activity. After a run-in period (15 days) of placebo treatment pts were assigned to two groups. The first (group A) continued placebo treatment for 30 days, the second (Group B) were given atenolol (ICI 66082) 100 mg daily for 30 days also. Atenolol significantly reduced systolic and diastolic blood pressure in recumbent and standing position and heart rate at rest. No significantly changes of the same parameters were observed in group A. Body weight and plasma renin activity was unchanged in both groups. Atenolol treatment never was discharged in order to side effects. These results seem to suggest that atenolol can be an useful drug in the treatment of systemic blood hypertension.
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PMID:[Efficacy and tolerability of a cardioselective beta-blocking drug (atenolol) in the treatment of essential hypertension. A double blind study (author's transl)]. 35 98

In pentobarbital-anesthetized rats, SK&F 87516 (1.25-80 micrograms/kg/min intravenously over 15 min), the fluoro analog of the selective DA-1 dopamine receptor agonist fenoldopam produced dose-related decreases in carotid artery blood pressure that faded during the infusion period. These effects were abolished by SCH 23390, prolonged by ritanserin, but unchanged by bilateral vagotomy, atenolol, ICI 118,551, idazoxan, methylatropine or S-sulpiride. SK&F 87516 also inhibited the hypotensive effects of clonidine and of the DA-1 receptor agonist fenoldopam, but not of acetylcholine. In pithed rats, SK&F 87516 produced a biphasic vasopressor response. The initial phase was enhanced by SCH 23390 and converted to a transient hypotension by idazoxan. The secondary response was inhibited by ritanserin and enalapril. In pithed, but not in intact rats, SK&F 87516 increased plasma renin activity. In intact rats, SK&F 87516 produced dose-related bradycardic effects that were inhibited (50%) by idazoxan, methylatropine or bilateral vagotomy and abolished by chlorisondamine or pithing. In pithed rats pretreated with either saline or idazoxan, SK&F 87516 reduced the tachycardia to electrical stimulation of preganglionic more than that to postganglionic cardioaccelerator nerve fibers. However, it did not modify heart rate increases evoked by intravenous norepinephrine. In conclusion, SK&F 87516 produces hypotension via vascular DA-1 receptor stimulation. The fading of this effect during the infusion of SK&F 87516 may be related to the partial agonist property of this compound at DA-1 receptors and the stimulation of 5-hydroxytryptamine-2 receptors. SK&F 87516 also behaves as a partial agonist at alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SK&F 87516, a close analog of fenoldopam, is a partial agonist at dopamine-1 and alpha-2 receptors and produces stimulation of 5-hydroxytryptamine-2 receptors in the cardiovascular system of the rat. 167 75

The beta-adrenoceptor antagonist pindolol [10-1,000 micrograms/kg subcutaneously (s.c.)] caused dose-related decreases in mean arterial pressure (MAP) and increased heart rate (HR) in conscious spontaneously hypertensive rats (SHR). The lowest dose of pindolol (10 micrograms/kg) decreased MAP by 25 mm Hg (-16%) without affecting plasma norepinephrine (NE) or plasma renin concentration (PRC). However, higher doses of pindolol elicited dose-related increases in plasma NE concentration and PRC. Plasma epinephrine concentration was not altered by pindolol. The selective beta 2-adrenoceptor antagonist ICI 118,551 (3 mg/kg, s.c.) prevented the tachycardia but not the increase in PRC caused by 100 micrograms/kg pindolol. Treatment with ICI 118,551 completely eliminated the 45% increase in plasma NE elicited by 100 micrograms/kg of pindolol even though the decrease in MAP caused by this dose of pindolol was the same in the presence (-33 mm Hg) and absence (-34 mm Hg) of beta 2-adrenoceptor blockade. These results indicate that the vasodepressor action of pindolol in SHR does not result from an agonistic effect at postjunctional beta 2-adrenoceptors in the vasculature. In addition, the increases in plasma NE concentration produced by pindolol result from stimulation of beta 2-adrenoceptors. These beta 2-adrenoceptors may be located prejunctionally on sympathetic neurons.
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PMID:Pindolol increases plasma norepinephrine concentration by stimulation of beta 2-adrenoceptors in conscious spontaneously hypertensive rats. 170 Feb 4

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
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PMID:Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure. 170 Feb 5

Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-performance liquid chromatography and radioimmunoassay. At basal state, BAECs contain angiotensin I, angiotensin II, and angiotensin III at concentrations of 2.5 +/- 1.3, 4.8 +/- 2.3, and 3.4 +/- 1.5 pg/10(6) cells, respectively. Angiotensin I, angiotensin II, and angiotensin III concentrations in the culture medium were 8.3 +/- 4.4, 9.4 +/- 3.5, and 9.9 +/- 3.3 pg/10(6) cells, respectively. Isoproterenol (0.1-10 microM) increases secretion of angiotensins I, II, and III in a dose-dependent manner. Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM). Forskolin (1-1,000 microM) mimics the isoproterenol-induced response. In contrast, alpha-adrenergic agonist phenylephrine (1-100 microM) inhibits the secretion. Pretreatment of BAECs with captopril (1 microM) inhibits the accumulation of angiotensin II and angiotensin III in the culture medium, but not angiotensin I. These findings suggest that BAEC production and/or secretion of angiotensins is regulated by adrenergic mechanisms.
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PMID:Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion. 215 59

The effect of a beta-adrenoceptor agonist on the release of the components of the vascular renin-angiotensin system was examined in vitro. Isolated rat mesenteric arteries were perfused in an open system with Krebs-Ringer solution and released immunoreactive angiotensin II (ANG IIir) into the perfusate was directly determined using a Sep-Pak C-18 cartridge connected to the perfusion system. Renin activity in the concentrated perfusate was also determined. Isoproterenol (1 nM-1 microM) increased the release of ANG IIir in a dose-dependent manner. The increase in ANG IIir release during isoproterenol (1 microM) infusion was inhibited by propranolol (1 microM) or captopril (2 microM). Isoproterenol-induced increment of ANG IIir release was blocked by the selective beta 2-adrenoceptor antagonist, ICI 118,551 (1 microM), but not by the selective beta 1-adrenoceptor antagonist, atenolol (1 microM). Renin activity in the perfusate was measurable, but did not increase in response to isoproterenol (1 microM) infusion. There was no significant difference in the response of ANG IIir release to isoproterenol between spontaneously hypertensive rats and Wistar-Kyoto rats. The present results indicate that locally generated ANG II is released by beta 2-adrenoceptor activation. The beta-adrenoceptor agonist and the vascular renin-angiotensin system may play an important role for the regulation of peripheral vascular tone.
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PMID:Role of vascular angiotensin II released by beta-adrenergic stimulation in rats. 243 81

1. The interaction between the vascular renin-angiotensin system and presynaptic beta-adrenoreceptors was examined in male and female normotensive and spontaneously hypertensive rats, using the in vitro perfused mesentery preparation. 2. Enhancement of the pressor response to periarterial nerve stimulation by isoprenaline was shown to be significantly greater in preparations from male and female spontaneously hypertensive rats compared to corresponding preparations from normotensive Wistar rats. 3. In preparations from normotensive and hypertensive animals, the potentiating effect of isoprenaline was prevented by pretreatment with propranolol or ICI 118 551, but not atenolol, implicating a beta 2-adrenoreceptor. 4. Angiotensin II enhanced the responses to peripheral nerve stimulation in preparation from normotensive and hypertensive animals. Enhancement was significantly greater in preparations from hypertensive animals. 5. The potentiation caused by isoprenaline was blocked by the angiotensin II receptor antagonist [Sar1-Ile8] angiotensin II, and by captopril. The potentiation following angiotensin II was unaffected by ICI 118 551. 6. These results suggest that stimulation of presynaptic beta 2-adrenoreceptors activates a localized angiotensin II system. No significant differences in this facilitatory system were observed between male and female animals, but the potentiation caused by activation of this system was considerably greater in the spontaneously hypertensive rats.
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PMID:Enhanced presynaptic facilitation of vascular adrenergic neurotransmission in spontaneously hypertensive rats. 256 99

We have previously shown that diphenylhydantoin (DPH)-stimulated renin release is mediated by, or requires the presence of, the renal nerves. In the present study, we examined the effects of adrenergic blockers in DPH-stimulated renin release in five groups of anesthetized dogs. In vehicle-treated dogs, DPH at a dose of 0.18 mg/kg-min increased renin secretion rate (RSR) from 56 +/- 14 to 269 +/- 60 and returned to 84 +/- 30 ng of angiotensin (ANG) l/hr-min (P less than 0.01, analysis of variance). In metoprolol-treated dogs, DPH produced no significant changes in RSR (90 +/- 28 to 144 +/- 67 to 100 +/- 51 ng of ANG l/hr-min). Likewise, in atenolol-treated dogs, RSR was 34 +/- 10 before, 59 +/- 15 during, and 23 +/- 8 ng of ANG l/hr-min after the infusion of DPH. In contrast, after pretreatment with ICI 118,551 (a beta 2 adrenoceptor antagonist), RSR was 37 +/- 9 before, 151 +/- 57 during, and 47 +/- 12 ng of ANG l/hr-min after the infusion of DPH (P less than 0.01). In phentolamine-treated dogs, RSR was 69 +/- 20 before, 295 +/- 53 during, and 95 +/- 17 ng of ANG l/hr-min after the infusion of DPH (P less than 0.01). Changes in renal blood flow, renal vascular resistance, and UNa V were in the same directions in all groups. These data suggest that DPH-stimulated renin release is mediated by beta 1 adrenoceptors since both beta 2 and alpha adrenoceptor antagonists have no effects on DPH-stimulated renin release.
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PMID:Role of adrenoceptors in diphenylhydantoin-stimulated renin release. 264 8

Both nonselective beta-blockers and beta 1-selective blockers are effective antihypertensive agents. beta 1-Blockade generally is considered to be responsible for their antihypertensive action, whereas beta 2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which beta-blockers lower blood pressure remains unknown. To examine the possibility that beta 2-blockade may contribute to the antihypertensive action of beta-blocker therapy, we studied the cardiovascular effects of compound ICI 118551, a beta 2-selective blocker. First, we showed that 50 mg t.i.d. orally is a beta 2-selective dose. In contrast to propranolol, 80 mg t.i.d., or atenolol, 100 mg once a day, 50 mg of ICI 118551 t.i.d. failed to block beta 1-mediated inotropic stimulation and stimulation of renin by isoproterenol. We then performed a double-blind, placebo-controlled trial in patients with mild essential hypertension to compare this compound with propranolol, 80 mg t.i.d., and showed that ICI 118551 significantly decreased systolic and diastolic blood pressure. This antihypertensive effect was demonstrated by direct as well as by indirect blood pressure measurements. Thus, contrary to prevailing thought, beta 2-blockade has an antihypertensive effect independent of, and distinct from, beta 1-blockade.
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PMID:Is beta 1-antagonism essential for the antihypertensive action of beta-blockers? 288 Aug 4


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